According to Penfold et al., Senile Macular Degeneration, Investigative Ophthalmology and Visual Science, 1986, 27, pp. 364-371, macular degeneration is one of the leading registered causes of blindness in the United States and in other Western countries.
Loss of central vision in macular degeneration occurs as a result of atrophy of the retinal pigment epithelium. There have been reports of histiocytic and giant cells in the areas of breaks in Bruch's membrane and subretinal neovascular membranes. Light and electron microscope studies of the atrophic cells in senile macular degeneration patients, carried out post mortem, show retinal epithelium cellular elements are destroyed, with the pigment being clumped and adhered to Bruch's membrane. These morphological studies suggest an inflammatory process induced by a degradation product or irritant in the area of the destroyed cells.
Macular degeneration of the retina is a progressive degeneration of the pigmented cells of the retina of unknown cause. The retina has a similar topographical layer arrangement of cytoarchitecture as the brain.
The six layers of the retina carry out the function of transmitting light stimuli into a neuronal excitation. The neuronal stimulus travels from the retinal structures through the optic nerve, then through the brainstem structure of the lateral geniculate, and thereafter through the optic radiations to the occipital final recipient special sensory cortical neurons.
The layers of the retina consist of a neuroectodermal layer of rods and cones, an intermediate layer of bipolar cells, horizontal cells and Muller's cells, and the inner layers containing ganglion cells, glia, nerve fibers, and internal limiting membrane.
The rods and cones are the photoreceptors and consist of outer segments of laminated plates of cells containing photoreceptive pigment and inner segments with dense packing of mitochondria.
The macula in the human retina has special cones and a dense concentration of ganglion cells which permit high resolution of visual acuity.
Pigmented cells occur in the red nucleus, substantia nigra, and locus coeruleus in the brain. The pigmented cells of the retina are hexagonal cells lying just externally to the rods and cones layer of the retina. These cells provide a sheathing or insulation of melanin pigment and also provide the Vitamin A substrate for the photosensitive pigments in the rod and cone cells.
Three forms of macular degeneration have been identified: the "dry" form, the "wet" form, and pigment epithelial detachment (PED). The dry form occurs in approximately 85 to 90% of patients with macular degeneration. The wet form, which can be more severe, occurs in only about 10% of patients. The PED occurs in less than 5% of the patients.
One of the most common forms of treatment for the wet form of macular degeneration is laser surgery. In the wet form of macular degeneration abnormal blood vessels grow under the retina and lift the retina up. These abnormal blood vessels are called subretinal neovascularization or SRNV. These abnormal blood vessels bleed, leak fluid, and lift up the retina. As a result, vision is reduced. A patient with this type of macular degeneration will lose ability to see unless laser treatment is promptly instituted. Abnormal blood vessels also may form in PED and laser surgery again is indicated here.
To date there has been no successful treatment of macular degeneration with pharmaceutical agents. According to a Symposium on Age-Related Macular Degeneration presented at a meeting of the Section on Ophthalmology of the New York Academy of Medicine, Dec. 7, 1987, moderated by Lawrence A. Yannuzzi, pp. 1-61, nutrition therapy has been used in treating macular degeneration. Copper, zinc, and selenium have been employed as have lipotriad and nicotinic acid. None of these agents really has proven to be successful.
Dimethyl sulfoxide also has shown potential in the prophylaxis against the development and progression of age-related macular degeneration. This agent has had clinical application as a scavenger for free radicals in the treatment of bladder cancer but no conclusion has been reached that the compound really is effective in the treatment of macular degeneration.
The compound L-deprenyl, a selective MAO-B inhibitor, has not been used heretofore in the treatment of macular degeneration. The indications of the compound include treatment of depression, Parkinson's Disease, and Alzheimer's Disease. See U.S. Pat. No. 4,861,800.